Diurnal rhythms in seizures detected by intracranial electrocorticographic monitoring: an observational study

Few studies have evaluated human seizure occurrence over the 24-hour day, and only one group has employed intracranial electrocorticography monitoring to record seizures. Circadian patterns in seizures may have important implications in diagnosis and therapy and provide opportunities in research. We have analyzed spontaneous seizures in 33 consecutive patients with long-term intracranial EEG and video monitoring. Several aspects of seizures were noted, including time of day, origin, type, and behavioral state (sleeping/awake). We recorded 450 seizures that showed an uneven distribution over the day, depending on lobe of origin: temporal lobe seizures occurred preferentially between 1100 and 1700 hours, frontal seizures between 2300 and 0500 hours, and parietal seizures between 1700 and 2300 hours. In the awake state, larger proportions of clinical seizures were seen from 0500 to 1100 hours and from 1700 to 2300 hours. During sleep, larger proportions occurred from 1100 to 1700 hours and from 2300 to 0500 hours. Our results suggest that seizures from different brain regions have a strong tendency to occur in different diurnal patterns

Chronotypes and subjective sleep parameters in epilepsy patients:A large questionnaire study

Accumulating evidence suggests epilepsy and seizures may influence circadian rhythms and that circadian rhythms may influence epilepsy. It is also conceivable that seizure timing influences the timing of daily activities, sleeping, and wakefulness (i.e., chronotype). Only one group has studied the distribution of chronotypes of epileptics, showing significant differences between the diurnal activity patterns in two groups of patients with different epilepsy syndromes. The authors performed a questionnaire-based study of 200 epilepsy patients to compare the distribution of chronotypes and subjective sleep parameters of sleep duration and time of mid-sleep on free days to the distribution in the general population (n = 4042). Within this large group of epilepsy patients, we also compared the chronotypes of subsamples with well-defined epilepsy syndromes, i.e., temporal lobe epilepsy [TLE; n = 46], frontal lobe epilepsy [FLE; n = 30], and juvenile myoclonic epilepsy [JME; n = 38]. In addition, 27 patients who had had surgery for TLE were compared with those with TLE who had not had surgery. Both the Morningness-Eveningness Questionnaire and Munich Chronotype Questionnaire were used to determine chronotypes and subjective sleep parameters. Significant differences in morningness/eveningness distribution, timing of mid-sleep (corrected for sleep duration), and total sleep time on free days were found between epileptics and healthy controls. Those with epilepsy were more morning oriented, had earlier mid-sleep on free days, and longer sleep duration on free days (p <.001). However, distributions of chronotypes and sleep parameters between the groups of people with TLE, FLE, and JME did not differ. Persons who had surgery for TLE had similar morningness-eveningness parameters and similar sleep durations compared to those without surgery, but mid-sleep on free days was earlier in operated patients (p = .039). In conclusion, this is the first large study focusing on chronotypes in people with epilepsy. We show that the distribution of chronotypes and subjective sleep parameters of epileptics, in general, is different from that of healthy controls. Nevertheless, no differences are observed between patients with specified epilepsy syndromes, although they exhibit seizures with different diurnal patterns. Our results suggest that epilepsy, itself, rather than seizure timing, has a significant influence on chronotype behavior and subjective sleep parameters. (Author correspondence: [email protected]

Multimodal nocturnal seizure detection: Do we need to adapt algorithms for children?

Objective: To assess the performance of a multimodal seizure detection device, first tested in adults (sensitivity 86%, PPV 49%), in a pediatric cohort living at home or residential care. Methods: In this multicenter, prospective, video-controlled cohort-study, nocturnal seizures were detected by heartrate and movement changes in children with epilepsy and intellectual disability. Participants with a history of >1 monthly major motor seizure wore Nightwatch bracelet at night for 3 months. Major seizures were defined as tonic–clonic, generalized tonic >30 s, hyperkinetic, or clusters (>30 min) of short myoclonic or tonic seizures. The video of all events (alarms and nurse diaries) and about 10% of whole nights were reviewed to classify major seizures, and minor or no seizures. Results: Twenty-three participants with focal or generalized epilepsy and nightly motor seizures were evaluated during 1511 nights, with 1710 major seizures. First 1014 nights, 4189 alarms occurred with average of 1.44/h, showing average sensitivity of 79.9% (median 75.4%) with mean PPV of 26.7% (median 11.1%) and false alarm rate of 0.2/hour. Over 90% of false alarms in children was due to heart rate (HR) part of the detection algorithm. To improve this rate, an adaptation was made such that the alarm was only triggered when the wearer was in horizontal position. For the remaining 497 nights, this was tested prospectively, 384 major seizures occurred. This resulted in mean PPV of 55.5% (median 58.1%) and a false alarm rate 0.08/h while maintaining a comparable mean sensitivity of 79.4% (median 93.2%). Significance: Seizure detection devices that are used in bed which depend on heartrate and movement show similar sensitivity in children and adults. However, children do show general higher false alarm rate, mostly triggered while awake. By correcting for body position, the false alarms can be limited to a level that comes close to that in adults

Wnt2 Regulates Progenitor Proliferation in the Developing Ventral Midbrain*

Wnts are secreted, lipidated proteins that regulate multiple aspects of brain development, including dopaminergic neuron development. In this study, we perform the first purification and signaling analysis of Wnt2 and define the function of Wnt2 in ventral midbrain precursor cultures, as well as in Wnt2-null mice in vivo. We found that purified Wnt2 induces the phosphorylation of both Lrp5/6 and Dvl-2/3, and activates β-catenin in SN4741 dopaminergic cells. Moreover, purified Wnt2 increases progenitor proliferation, and the number of dopaminergic neurons in ventral midbrain precursor cultures. In agreement with these findings, analysis of the ventral midbrain of developing Wnt2-null mice revealed a decrease in progenitor proliferation and neurogenesis that lead to a decrease in the number of postmitotic precursors and dopaminergic neurons. Collectively, our observations identify Wnt2 as a novel regulator of dopaminergic progenitors and dopaminergic neuron development

PMS2 Involvement in Patients Suspected of Lynch Syndrome

It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene, PMS2, play a far more important role in Lynch syndrome than initially thought. To explore this further, we determined the prevalence of pathogenic germline PMS2 mutations in a series of Lynch syndrome-suspected patients. Ninety-seven patients who had early-onset microsatellite instable colorectal or endometrial cancer, or multiple Lynch syndrome-associated tumors and/or were from an Amsterdam Criteria II-positive family were selected for this study. These patients carried no pathogenic germline mutation in MLH1, MSH2, or MSH6. When available, tumors were investigated for immunohistochemical staining (IHC) for PMS2. PMS2 was screened in all patients by exon-by-exon sequencing. We identified four patients with a pathogenic PMS2 mutation (4%) among the 97 patients we selected. IHC of PMS2 was informative in one of the mutation carriers, and in this case, the tumor showed loss of PMS2 expression. In conclusion, our study confirms the finding of previous studies that PMS2 is more frequently involved in Lynch syndrome than originally expected. (C) 2009 Wiley-Liss, Inc

Multimodal nocturnal seizure detection in a residential care setting:a long-term prospective trial

\u3cp\u3eObjective To develop and prospectively evaluate a method of epileptic seizure detection combining heart rate and movement. Methods In this multicenter, in-home, prospective, video-controlled cohort study, nocturnal seizures were detected by heart rate (photoplethysmography) or movement (3-D accelerometry) in persons with epilepsy and intellectual disability. Participants with &gt;1 monthly major seizure wore a bracelet (Nightwatch) on the upper arm at night for 2 to 3 months. Major seizures were tonic-clonic, generalized tonic &gt;30 seconds, hyperkinetic, or others, including clusters (&gt;30 minutes) of short myoclonic/tonic seizures. The video of all events (alarms, nurse diaries) and 10% completely screened nights were reviewed to classify major (needing an alarm), minor (needing no alarm), or no seizure. Reliability was tested by interobserver agreement. We determined device performance, compared it to a bed sensor (Emfit), and evaluated the caregivers' user experience. Results Twenty-eight of 34 admitted participants (1,826 nights, 809 major seizures) completed the study. Interobserver agreement (major/no major seizures) was 0.77 (95% confidence interval [CI] 0.65-0.89). Median sensitivity per participant amounted to 86% (95% CI 77%-93%); the false-negative alarm rate was 0.03 per night (95% CI 0.01-0.05); and the positive predictive value was 49% (95% CI 33%-64%). The multimodal sensor showed a better sensitivity than the bed sensor (n = 14, median difference 58%, 95% CI 39%-80%, p &lt; 0.001). The caregivers' questionnaire (n = 33) indicated good sensor acceptance and usability according to 28 and 27 participants, respectively. Conclusion Combining heart rate and movement resulted in reliable detection of a broad range of nocturnal seizures.\u3c/p\u3